کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1922754 | 1048831 | 2006 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The pathological role of Pael-receptor/GPR37 in AR-JP
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The pathological role of Pael-receptor/GPR37 in AR-JP The pathological role of Pael-receptor/GPR37 in AR-JP](/preview/png/1922754.png)
چکیده انگلیسی
Autosomal recessive juvenile parkinsonism (AR-JP) is caused by mutations in the parkin gene. Parkin is a ubiquitin ligase that ubiquitinates and promotes the proteasome-mediated degradation of its substrate protein. Therefore, the accumulation of the substrate(s) of Parkin is thought to lead to AR-JP. We have identified Pael receptor (Pael-R) as a specific substrate of parkin. Pael-R is a G-protein-coupled orphan receptor that is highly expressed in dopaminergic neurons in the substantia nigra. Correct folding of Pael-R protein is difficult and approximately half of newly synthesized Pael-R becomes misfolded, and is ubiquitinated by Parkin and degraded via the ubiquitin-proteasome system. Inhibition of degradation of overexpressed Pael-R in cultured cells leads to the accumulation of misfolded Pael-R in the endoplasmic reticulum (ER) and induces ER stress, followed by cell death. Pan-neuronal overexpression of Pael-R in the Drosophila brain induces age-dependent selective degeneration of dopaminergic neurons. Based on these results, we hypothesize that accumulation of a parkin substrate, misfolded Pael-R, plays a crucial role in the pathogenesis of AR-JP.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Parkinsonism & Related Disorders - Volume 12, Supplement 2, October 2006, Pages S110-S113
Journal: Parkinsonism & Related Disorders - Volume 12, Supplement 2, October 2006, Pages S110-S113
نویسندگان
Ryosuke Takahahshi,